1. Field of the Invention:
This invention relates to a process for preparation of valuable antimicrobial agents. More particularly, it relates to the process for the preparation of quinoline carboxylic acid derivatives.
2. Description of the Prior Art:
Previously, the present inventors made clear that 1-ethyl-6-fluoro-7-(1-piperazinyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid has more potent antimicrobial activities than the known antimicrobial agents, and reported the process for the preparation of the above compound, simultaneously (Japanese Laid-Open Patent Application No. Sho 53-141286). Also, the preparations of 1-ethyl-6-fluoro-7-(4-methyl-1-piperazinyl)-4-oxo-1,4-dihydroquinoline-3-c arboxylic acid and the related compounds were reported by the present inventors (Japanese Laid-Open Patent Application No. Sho 54-138582, No. Sho 55-40656 and No. Sho 55-47658). Further, many substituted quinoline carboxylic acids and their preparation have been also stated by Pesson (France) in Japanese Laid-Open Patent Application No. Sho 54-66686.
In the above prior arts, the antimicrobial agents [IV] are prepared by the reaction of the corresponding carboxylic acid [V], ##STR3## wherein R.sub.1 is defined as above, with the compound [II]. In this method, the purity of the starting material [V] and the reaction condition exert an awful influence upon the yield of the purified product [IV].
Namely, the purification of the material [V] is difficult because of its slight solubility in various kinds of solvents, so it is hard to obtain pure material [V] in industrial scale. Furthermore, even if the purified material [V] is used in the reaction with the compound [II], a following compound [VI], ##STR4## wherein R.sub.1 and R.sub.4 are defined as above, is produced as a by-product. The formation of the by-product causes lowering of the yield of the purified product [IV].